CATT Results Released: Avastin and Lucentis Equivalent for AMD

Well, it’s the big news today. The one-year results of the NIH sponsored CATT trial, comparing Avastin (bevacizumab) and Lucentis (ranibizumab) in a head-to-head comparison for the treatment of AMD were released early. The results at one year show equal efficacy in terms of visual acuity. Interestingly, the study also show that prn dosing results in equal visual acuities when compared to monthly dosing.

Here are the key paragraphs from the NIH press release. The full article is available online at the NEJM site, if you have access to that site.

“NEI launched CATT in 2008 to compare Lucentis and Avastin for treatment of wet AMD. The study has now reported results for 1,185 patients treated at 43 clinical centers in the United States. Patients were randomly assigned and treated with one of four regimens for a year. They received Lucentis monthly or PRN, or Avastin monthly or PRN. Enrollment criteria required that study participants had active disease.

“Patients in the monthly dosing groups received an initial treatment and then had an injection every 28 days. Patients in the PRN groups received an initial treatment and were then examined every 28 days to determine medical need for additional treatment. PRN groups received subsequent treatment when there were signs of disease activity, such as fluid in the retina. Ophthalmologists involved in patient care did not know which study drug a patient was getting, to make sure that the data was not affected by how anyone felt about the treatment.

“Change in visual acuity served as the primary outcome measure for CATT. Thus far, visual acuity improvement was virtually identical (within one letter difference on an eye chart) for either drug when given monthly. In addition, no difference was found in the percentage of patients who had an important gain or loss in visual function. Also, when each drug was given on a PRN schedule, there also was no difference (within one letter) between drugs. PRN dosing required four to five fewer injections per year than monthly treatment. Visual gains were about two letters less with PRN than with monthly treatment but overall visual results were still excellent.

“‘In addition to the primary finding of equivalence between Lucentis and Avastin for visual acuity, CATT also demonstrates that PRN dosing is a viable treatment option for either of these drugs,’ said Daniel F. Martin M.D., study chair for CATT and chairman of the Cole Eye Institute at the Cleveland Clinic. ‘Substantial visual acuity gains may be accomplished with a lower treatment burden.’

“Adverse events indicate development or worsening of a medical condition. They may or may not be causally associated with the clinical trial treatment, but they are always monitored and reported in any clinical trial. The median age of patients in CATT was over 80 years, and a high rate of hospitalizations might be anticipated as a result of chronic or acute medical conditions more common to older populations.

“Serious adverse events (primarily hospitalizations) occurred at a 24 percent rate for patients receiving Avastin and a 19 percent rate for patients receiving Lucentis. These events were distributed across many different conditions, most of which were not associated with Avastin in cancer clinical trials where the drug was administered at 500 times the dose used for AMD. The number of deaths, heart attacks, and strokes were low and similar for both drugs during the study. CATT was not capable of determining whether there is an association between a particular adverse event and treatment. Differences in serious adverse event rates require further study.

“Investigators in the CATT study will continue to follow patients through a second year of treatment. These additional data will provide information on longer-term effects of the drugs on vision and safety.

Lucentis vs Avastin: Who will win the race?

As we await the results of the NIH sponsored CATT trial, a head-to-head comparison of ranibizumab (Lucentis) and bevacizumab (Avastin), other smaller studies are trickling in, pointing to what many of us suspect from clinical experience — their efficacy is pretty much the same. Fong et al. published a study in the February issue of Ophthalmology (Intravitreal bevacizumab and renibizumab for age-related macular degeneration) which compared the results from 342 pateints treated with bevacizumab and 128 with ranibiumab. It was a non-randomized trial and the bevacizumab patients were younger. The study showed that both groups had fairly equal results at 12 months. About 23% of bevacizumab patients and 25% of ranibizumab patients had visual acuity of 20/40 or better. More patients with bevacizumab (27%) had improved vision compared to ranibizumab (20%). So, I think we can call it close to even, and remember that about 25% will have improvement of vision and the same percentage with get to 20/40 or better.

The one point that stood out was that in a year, the bevacizumab patients needed about 4 injections, whereas the ranibizumab patients needed 6 injections. This is in keeping with the thought that bevacizumab, being a larger molecule, stays around longer and has a longer duration of action.

Which brings us to the road ahead. The fact that the CATT study has not been stopped, points to the fact that bevacizumab is likely not either significantly less effective or more dangerous than its $2000 per dose cousin, ranibizumab. Both drugs are made by Genentech, bevacizumab being the off-label one. It’s tough for a company to have two of its drugs competing against one another, especially if the off-label one wins or comes close to being even. I believe that Genentech’s approach in the coming years will be to make ranibizumab easier to use. The concern with both these drugs is the ongoing burden of repeat injections. We have a history of the development of sustained-release intraocular drugs in ophthalmology, and the next step is to get one of these drugs into a sustained release form to decrease the number of injections required. Genentech will develop ranibizumab in a sustained release form, leaving bevacizumab to be injected repeatedly. So the issue of equal efficacy will become moot.

Bilateral same-day intravitreal injections? Yes!

One of the growing issues in treating age-related macular degeneration (AMD) is to reduce the burden of treatment for the patients, many of whom are elderly, and may require injections of VEGF inhibitors every 4-8 weeks. A long-standing tradition in ophthalmology has been to avoid bilateral same-day surgical intervention. The rationale has been that if you operate on two eyes on the same day, any infection that develops in one eye may spread to the other eye, and that if there is any contamination of instruments or compounds used during the surgery, operating on both eyes on the same day increases the likelihood that both eyes will be adversely affected.

Intravitreal injections, which have become standard of care for treatment of AMD are fairly innocuous in terms of surgical insult. The “wound” is a 31 gauge needle entry site. Nevertheless, endophthalmitis may develop. For example, in the VISION study of intravitreal pegaptanib, the incidence of endophthalmitis was 0.16%. In the MARINA study of intravitreal ranibizumab, it was 0.05%. And in the ANCHOR study of ranibizumab, it was 0.05% (3 cases our of 5,921 injections). A study by Pilli et all reported an incidence of 0.029% (3 cases in 10,254 injections). These incidences were for unilateral injections.

So, is there an increased risk for bilateral same-day injections? Lima et al (Yannuzzi’s group) out of New York published their retrospective analysis of bilateral same-day intravitreal injections of VEGF inhibitors in the October 2009 issue of Retina. They report that of 1,534 bilateral injections (3,068 injections total), the incidence of culture-proven endophthalmitis was 0.065%, and the incidence of acute intraocular inflmaation was 0.033%. None of those cases were bilateral. There were no cases of retinal breaks. They conclude that it appears that there is no increased risk for same-day bilateral injections of VEGF inhibitors, as the complication rates are similar.

It’s noteworthy that all patients in their study were done in the office, and received surface disinfection with 5% providone-iodine solution, followed by 2 days of either polytrim or ofloxacin qid.

The study is very useful and gives comfort to those of us considering bilateral same-day injections. In any disease process where the incidence of an occurence is very low, large numbers of patients are needed to determine whether or not there is a difference in incidence between groups, and so, it is fair to say that there is no obvious increase in the risk of complications from bilateral VEGF inhibitor injections, while recognizing the limitation of the comparison.

Bevacizumab helpful in BRVO

The SCORE study showed that intravitreal triamcinolone was no more helpful than standard therapy (macular laser) in improving vision in patients with branch retinal vein occlusions (BRVO), and thus the SCORE study concluded to continue using standard therapy to treat BRVO.  The question is, might another agent, say a VEGF inhibitor like bevacizumab (Avastin) be helpful in treating BRVO?

We get some indirect answers in a study published in the November/December issue of Retina.  The study (Comparison of two doses of intravitereal bevacizumab as primary treatment for macular edema secondary to branch retinal vein occlusion:  results of the pan american collaborative retina study group at 24 months) by Wu et al and the Pan-American Collaborative Retina Study Group was a retrtospective multicenter study looking at results from 63 eyes treated with two different doses of bevacizumab:  1.25 mg and 2.5 mg.  Other studies had shown benefit in visual acuity and central macular thickness (CMT) with bevacizumab in BRVO, and the authors wondered if an increased dose may improve the visual outcome or decrease the frequency of injections.  Patients with macular edema were given bevacizumab at one of the two doses (depending on the center they visited) and were examined on a monthly basis.  OCT’s were performed at months 1, 3, 6, 12 and 24.  If at any time the OCT measured CMT > 250 microns, they were classified as “recurrent” or “persistent” macular edema, and were re-injected.  Re-injections were also given if visual acuity decreased by more than 5 letters (1 line).

Their study found that there was no additional benefit from the higher dose, and that both groups experienced improved vision and decreased CMT.  The results showed that on average, CMT improved from about 450 mic at the first visit, to 250 mic at 3 months, and ended up at the 240 mic range at 24 months.  Furthermore, the mean time for repeat injections was in the 10-13 week range.

But is this better than laser?  Well, the study doesn’t directly look at this question, but it does state that among its small sample size of 63 eyes, of those receiving 1.25 mg, 68% experienced improvement in vision by 3 or more lines of vision (72% in the 2.5 mg group).  That’s pretty significant percentage of improved vision.  You’ll recall that the SCORE Study patients had improved vision in the 26-29% range for IVTA and laser.  So bevacizumab seems to give better results than laser for BRVO.  I realize I’m mixing studies — not really a meta-analysis (maybe a “mini”-analysis), and clearly this needs to be studied further.  But the authors seem to lay out a reasonable approach for treating BRVO with bevacizumab, and their results seem to be significantly better than best results we have available with laser or IVTA.  Check vision monthly, and if worse by 5 letters, treat with bevacizumab;  check OCT at 3, 6 12 and 24 mo, and if CMT > 250 treat with bevacizumab.  Expect about 70% to improve 3 or more lines of vision.

Is Avastin the new laser for diabetic macular edema?

In the June 2009 issue of Ophthalmology Soheilian et al, out of Tehran, published an important paper comparing intravitreal bevacizumab (IVB) alone or in combination with triamcinolone (+IVTA) to macular photocoagulation for treatment of diabetic macular edema.  They randomized a total of 150 eyes with clinically significant macular edema (CSME) into three treatment groups, and followed them for up to 36 weeks (which is about 9 months).   If CSME persisted at 12 week (3 mo) intervals, the eye were retreated with the same intervention.  Their study showed that intravitreal bevacizumab yielded better visual acuity results at 36 weeks than did laser treatment.  Specifically, vision improved by > 2 Snellen lines of acuity in 37% of the IVB group, 25% of the IVB+IVTA group, and 15% of the laser group.  On the other hand, retreatment was required in 28%, 20% and 6% of the three groups respectively.  IVB improves vision more, but needs to be used more often.

One of the things that the study did not do, was differentiate the patients with CSME into those with cystic edema and those with non-cystic edema.  My hunch is that we would find that in the group with cystic edema, the difference between the effectiveness in bevacizumab and laser would be even greater.  Will bevacizumab become a replacement for laser in treating CSME?  It’s too soon to say.  My hope is that the Sohelian et al will continue to follow these patients and report on results as they reach the 1 year and 2 year marks.

In clinical practice, this paper seems to support what many of us are currently doing:  using bevacizumab as first line treatment for diabetic macular edema to decrease the edema and improve the vision, and following it up with laser treatment for long term control.  I’d like to see a study that looks at this situation.  I use the sequential approach with greatest success in patients with massive or cystic macular edema.

Here is the abstract:

Ophthalmology. 2009 Jun;116(6):1142-50. Epub 2009 Apr 19.

Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema.

Soheilian M, Ramezani A, Obudi A, Bijanzadeh B, Salehipour M, Yaseri M, Ahmadieh H, Dehghan MH, Azarmina M, Moradian S, Peyman GA.

Ophthalmology Department, Labbafinejad Medical Center, Shaheed Beheshti Medical University, Tehran, Iran. masoud_soheilian@yahoo.com

PURPOSE: To compare the results of intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal triamcinolone acetonide (IVT) versus macular laser photocoagulation (MPC) as a primary treatment of diabetic macular edema (DME). DESIGN: Randomized 3-arm clinical trial. PARTICIPANTS: A total of 150 eyes of 129 patients with clinically significant DME and no previous treatment.

METHODS: The eyes were randomly assigned to 1 of the 3 study arms: the IVB group, patients who received 1.25 mg IVB (50 eyes); the IVB/IVT group, patients who received 1.25 mg of IVB and 2 mg of IVT (50 eyes); and the MPC group, patients who underwent focal or modified grid laser (50 eyes). Retreatment was performed at 12-week intervals whenever indicated. MAIN OUTCOME MEASURES: Change in best-corrected visual acuity (VA) at week 24.

RESULTS: VA changes among the groups were statistically significant at 6 (P<0.001) and 24 (P = 0.012) weeks. The significant treatment effect was demonstrated in the IVB group at all follow-up visits and in the IVB/IVT group at 6 and 12 weeks. VA changes +/- standard deviation at 36 weeks were -0.28+/-0.25, -0.04+/-0.33, and +0.01+/-0.27 logarithm of minimum angle of resolution in the IVB, IVB/IVT, and MPC groups, respectively (P = 0.053). Significant central macular thickness (CMT) reduction was observed in all groups only up to 6 weeks; however, CMT changes were not significant among the groups in all visits. Overall, retreatment was required for 27 eyes up to 36 weeks (14 in the IVB group, 10 in the IVB/IVT group, and 3 in the MPC group). In the IVB group, in which a greater VA improvement was observed, only 1 injection was required in 72% of the cases. VA improvement >2 Snellen lines at 36 weeks was detected in 37%, 25%, and 14.8% of patients in the IVB, IVB/IVT, and MPC groups, respectively.

CONCLUSIONS: Intravitreal bevacizumab injection in patients with DME yielded a better visual outcome at 24 weeks compared with macular photocoagulation. A change in CMT beyond the 6-week time point that corresponded to the vision change was not detected. No adjunctive effect of IVT was demonstrated.

ANCHOR Study: Lucentis is better than Photodynamic Therapy for Classic ARMD

Here’s the abstract for the two-year study results.  There are a few key points:  Ranibizumab patients maintained vision better (90%) vs. PDT patients (65%).  More ranibizumab patients gained vision (about 35-40%) than PDT patients (6%).  Injections were monthly.

Ophthalmology. 2009 Jan;116(1):57-65.e5.
Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study.
Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T; ANCHOR Study Group.

Collaborators (87)
Vitreoretinal Consultants, Methodist Hospital, Houston, Texas 77030, USA. dmbmd@houstonretina.com
Comment in:

Ophthalmology. 2009 Aug;116(8):1593.
OBJECTIVE: The 2-year, phase III trial designated Anti-vascular endothelial growth factor (VEGF) Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization (CNV) in Age-related Macular Degeneration (ANCHOR) compared ranibizumab with verteporfin photodynamic therapy (PDT) in treating predominantly classic CNV. DESIGN: Multicenter, international, randomized, double-masked, active-treatment-controlled clinical trial. PARTICIPANTS: Patients with predominantly classic, subfoveal CNV not previously treated with PDT or antiangiogenic drugs.

INTERVENTION: Patients were randomized 1:1:1 to verteporfin PDT plus monthly sham intraocular injection or to sham verteporfin PDT plus monthly intravitreal ranibizumab (0.3 mg or 0.5 mg) injection. The need for PDT (active or sham) retreatment was evaluated every 3 months using fluorescein angiography (FA). MAIN OUTCOME MEASURES: The primary, intent-to-treat efficacy analysis was at 12 months, with continued measurements to month 24. Key measures included the percentage losing <15 letters from baseline visual acuity (VA) score (month 12 primary efficacy outcome measure), percentage gaining >or=15 letters from baseline, and mean change over time in VA score and FA-assessed lesion characteristics. Adverse events were monitored.

RESULTS: Of 423 patients (143 PDT, 140 each in the 2 ranibizumab groups), the majority (>or=77% in each group) completed the 2-year study. Consistent with results at month 12, at month 24 the VA benefit from ranibizumab was statistically significant (P<0.0001 vs. PDT) and clinically meaningful: 89.9% to 90.0% of ranibizumab-treated patients had lost <15 letters from baseline (vs. 65.7% of PDT patients); 34% to 41.0% had gained >or=15 letters (vs. 6.3% of PDT group); and, on average, VA was improved from baseline by 8.1 to 10.7 letters (vs. a mean decline of 9.8 letters in PDT group). Changes in lesion anatomic characteristics on FA also favored ranibizumab (all comparisons P<0.0001 vs. PDT). Overall, there was no imbalance among groups in rates of serious ocular and nonocular adverse events. In the pooled ranibizumab groups, 3 of 277 (1.1%) patients developed presumed endophthalmitis in the study eye (rate per injection = 3/5921 [0.05%]).

CONCLUSIONS: In this 2-year study, ranibizumab provided greater clinical benefit than verteporfin PDT in patients with age-related macular degeneration with new-onset, predominantly classic CNV. Rates of serious adverse events were low. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Bevacizumab speeds resolution of vitreous hemorrhage

A study in the September 2009 issue of Retina by Huang et al. out of Taiwan is titled “Intravitreal Bevacizumab and Panretinal Photocoagulation for Proliferative Diabetic Retinopathy Associated with Vitreous Hemorrhage.”  In this important study, they took 40 patients with vitreous hemorrhage (VH) too dense to treat with PRP, and if the VH  did not clear within two weeks, they treated them with bevacizumab (Avastin).  If the VH did not clear, they treated again in 4-6 weeks.  If the VH heme had not cleared by 12 weeks, they performed a pars plana vitrectomy (PPV).  They compared this to a group of 40 patients who did not receive bevacizumab.  When the vitreous was clear enough in either group, they received PRP.

The results showed that patients receiving bevacizumab cleared anywhere from 2-20 weeks (avg 12 weeks), whereas the patients who did not receive bevacizumab required 6-30 weeks (avg 18 weeks) to clear.  Only 10% of those receiving bevacizumab required PPV, whereas 40% of those who did not receive the drug required PPV.

So, clearly, intravitreal bevacizumab is helpful in the initial treatment of VH from proliferative diabetic retinopathy.  It improves the rate of resolution of VH, and decreases the need for surgery.  Two points were of interest to me.  Neither was specifically studied in the paper, but the authors raise the issues in their study design .  First, they remind us that bevacizumab can induce a fibrous response (“Avastin crunch”) and lead to tractional retinal detachments, and so they excluded patients whose ultrasounds showed the presence of tractional detachments or fibrous responses.  They repeated the B-scans as they followed the injected patients to watch for tractional detachments.  Second, they chose 4-6 weeks as the interval for re-injection of bevacizumab. They based this on two previous papers.  One by Jorge et al. which showed that peak regression of NV in diabetic retinopathy occured at 6 weeks, and that by 12 weeks, leakage had resumed; and the other by Arevalo et al. which showed that regression of NV could occur as quickly as 7-15 days after injection of bevacizumab.

Pearls to take away:  Inject bevacizumab for dense vitreous hemorrhages, get a baseline B-scan and follow the B-scans after injection for tractional detachments, and consider re-injections at 4-6 weeks.

Improving intravitreal injections

Have you ever noticed that when you give an intravitreal injection of bevacizumab, or some other drug, a bleb seems to rise on the conjunctiva immediately after injection?  Presumably, that bleb is reflux of the drug (or vitreous).  One way to avoid this, is to simply start the injection at a 30 degree angle to the tangent to the globe.  Just as the needle enters the sclera, turn the needle so it is going straight in (90 degrees to the tangent), and then enter the vitreous.  This effectively creates a “bi-planar” path of the needle, and reduces reflux of the drug.

The technique is described briefly in the September 2009 issue of Retina in an article by Pascal Knecht et al. out of Switzerland.  In their study, they compared the straight ahead injection to the “bi-planar” injection (which they call “tunneled”, but they’re both tunneled, aren’t they?).  They looked at three parameters after injection 0.05 mL of bevacizumab: rise in intraocular pressure, amount of vitreous reflux, and patient discomfort.  The IOP increased more in the tunnelled group (avg 35 mmHg) vs. the straight group (avg 30 mmHg), but after 5 minutes there was no IOP difference between the two groups.  After 15 minutes, both groups were less than 30 mmHg.  Good news on that front.

The amount of vitreous reflux was measured by documenting the width of the broadest conjunctival elevation at the injection site, i.e. the width of the bleb.  They were graded as either 1mm, 2mm, and >2mm.  Not surprisingly, the straight technique had more reflux.  20/30 patients in the straight group had reflux, whereas only 8/30 in the tunneled group had reflux.  The amount of reflux was also more in the straight group.

Finally, there was no difference in pain between the two groups.

Since reading this article, I’ve started the bi-planar “tunneled” technique.  The key is to turn the needle from 30 degrees to 90 degrees while the needle is only partially through the sclera.  I’ve also found it helps prevent reflux to withdraw the needle slowly after the injection, and I actually turn the needle back to the 30 degree angle as the tip emerges from the globe.

Head-to-head Lucentis vs. Avastin Trials

This bit of news just came in from the annual meeting of the American Academy of Ophthalmology, which is being held right now in San Francisco. There is a lot happening in terms of these two drugs. The results will be important, both clinically and economically. Lucentis costs $2,000 per dose. Avastin costs less than 10% per dose. Both drugs are made by Genentech — that’s a whole different story. Here is a list of current clinical trials as described in the article from “Academy Live” email from Friday October, 23, 2009, a service of the American Academy of Ophthalmology.

Bevacizumab vs. ranibizumab: Initial results expected in 2011
Bevacizumab (Avastin) and ranibizumab (Lucentis) are competing in a hefty schedule of six head-to-head randomized clinical trials directly comparing their use in AMD patients, said Daniel F. Martin, MD. This year, researchers hope to complete enrollment in the studies, which compare varying doses and treatment schedules of the drugs. Initial study results are expected to be available in early 2011, Dr. Martin said.

Here’s the status of each of the studies:

• The NEI-sponsored CATT (Comparison of AMD Treatments Trial) study began enrolling an estimated 1,200 wet AMD patients at 44 sites in the United States in February 2008. The four-arm study comparing bevacizumab and ranibizumab on fixed and variable schedules is proceeding well, according to Dr. Martin, with one-year results targeted for 2011.
• In April 2008, researchers in the United Kingdom began enrolling an anticipated 600 patients at 17 sites in the IVAN (Inhibit VEGF in Age-related choroidal Neovascularization) study. This four-armed study compares monthly bevacizumab 1.25 mg and ranibizumab 0.5 mg injections given over two years with three monthly injections followed by PRN dosing.
• The four-site German VIBERA study started enrolling 360 AMD patients in 2008 to receive three monthly bevacizumab 2.0 mg or ranibizumab 0.5 mg injections and additional injections as needed.
• The Austrian MANTA study began assigning an anticipated 320 AMD patients in June 2008 to three monthly bevacizumab or ranibizumab injections, with additional treatment as needed.
• Researchers in Norway began enrolling an anticipated 450 patients in the 12-site LUCAS study in March. Subjects receive bevacizumab 1.25 mg or ranibizumab 0.5 mg monthly as needed until dry, with intervals between doses decreasing over time.
• French investigators opened enrollment this fall in the 600-patient, 20-site GEFAL study. Subjects are randomized to receive three initial monthly injections of one of the two drugs.

Risk of Stroke with Lucentis vs. Avastin

In the February 2009 issue of Ophthalmology, a meta-analysis was reported in a letter to the editor pointing out some risks associated with intravitreal injection of ranibizumab (Lucentis). The letter looked at pooled data from the MARINA, ANCHOR and FOCUS studies which were done to determine effectiveness and adverse effects of Lucentis. The authors of the letter point out that when pooling all the data, the ranibizumab group had a 2.2% incidence of stroke, whereas the control group had a 0.7% incidence of stroke. They conclude that the risk of stroke rises as a result of ranibizumab treatment. When they look at the incidence of myocaridal infarction (MI), the ranibizumab group had a 1.9% incidence whereas the control group had a 3.0% incidence. They did not “conclude” that intravitreal injection was protective for MI, but the incidence is lower in the group receiving the drug vs. the control group.

Since the letter was published, there has been some discussion regarding the implications of this meta-analysis for those of us using Avastin. At the current time the feeling is that this data cannot be extrapolated to Avastin, in part because Avastin is a larger molecule (the entire globulin, vs. the immune arms as with ranibizumab). This molecular characteristic is felt to result in less egress of Avastin into the systemic circulation, and it is to this characteristic that the longer-acting effect of Avastin has been attributed. There is currently an NIH sponsored head-to-head clinical trial comparing Lucentis and Avastin underway. The results are due in 2012. The study is ongoing, and the fact that it has not been stopped is some solace to those of us who prefer Avastin that the study has not to date shown that Avastin is either hugely inferior or has significantly higher side-effects that Lucentis.